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In microbial fermentations to produce metabolites, at least 33% of the sugar-substrate carbon is lost as CO2 during pyruvate decarboxylation to acetyl-CoA. Previous attempts to reduce this carbon loss focused on engineering a single organism. In nature, microorganisms live in complex communities where syntrophic interactions result in superior resource utilization. Microbial communities are ubiquitous in nature and have a wide range of applications, including production of biofuels and chemicals. Syntrophic and other microbial co-cultures/consortia carry out efficient bio-transformations that are the result of multiple complementary metabolic systems working together. It is now well appreciated that the capabilities of multi-microorganism systems cannot be predicted by the sum of their parts. Rather, synergistic interactions at different levels often result in better overall performance of these systems. Importantly, integration of diverse metabolic systems through syntrophic dependencies make co-culture systems robust to environmental fluctuations. Clostridium organisms are of major importance for developing new technologies to produce biofuels and chemicals. Three major types of Clostridium organisms have been the focus of studies for the sustainable production of fuels and chemicals. Solventogenic clostridia utilize a large variety of biomass-derived carbohydrates (hexoses, pentoses, disaccharides, and hemicellulose), and can produce C2-C4 chemicals. Acetogenic clostridia can fix inorganic H2, CO2, and CO to generate C2 acids and alcohols. Other specialized clostridia possess diverse biosynthetic capabilities for production of a wide …